It has been postulated that the prefrontal cortices of schizophrenic patients have less interneuronal space than controls, specifically in areas 9 and 46. This is thought to reflect an alteration in the neuronal circuitry of these areas that according to Selemon et al. (1995) is a possible component of the pathology of schizophrenia. This study, and those that followed, were based on measures of neuronal density. Our goal is two-fold: one is to examine this finding based on the cortical minicolumn, and secondly, to elucidate the distribution of interneuronal space in regards to the morphology of the cell column. Our preliminary study used a small population of normal controls (n = 16) and schizophrenic patients (n = 9), diagnosed according to DSM ffl-R criteria. Our test revealed smaller values for all spacing distances and neuropil space in area 9 of schizophrenic brains. The greatest reduction occurred in the minicolumn compartment where the majority of apical dendrite bundles, thalamocortical, and cortico-cortical fibers are found. This study will examine columnar differences in 40 schizophrenic (DSM IV diagnosis) and 52 controls derived from the Runwell ifi collection. Specimens will be derived from areas 9, 46, 17, and 4 (Brodmann). Magnified images (lOOx) of Nissi-stained cell columns in layers III-VI will be analyzed by powerful computer imaging hardware and software enabling researchers to precisely quantify details of cell column morphology. Stereological techniques will be used to estimate neuronal density. If our preliminary findings are corroborated, the smaller than normal minicolumns will demonstrate a reorganization of brain circuitry most probably defined during development.